The biology of the model nematode Caenorhabditis elegans is probably understood in more detail than that of any other animal species. Furthermore, classical and molecular genetic studies, the recent success in cloning (very nearly) the entire genome and the initiation of a concerted effort to sequence the genome increase the value of this system even further. A consequential deduction from studies of C. elegans is that most fundamental aspects of the biology of this nematode are closely related, at the molecular level, to those operating in other animal species, including man. Consistent with this conclusion, about half of the genes cloned from C. elegans have been found to be homologous to previously known human genes. Other seemingly important C. elegans genes have no known homologues. Many of these genes are likely to have undiscovered human homologues whose identification can have a substantial impact on studies of human disease: Alterations of these genes may contribute to the pathophysiology of human disease. Other homologues may identify new human genes that become novel human therapeutics or provide target-directed screens for the discovery of new therapeutics. The goal of the present research is to develop tools for the systematic identification of human homologues of C. elegans genes.